The use of thin films and sheets in drug delivery has developed and matured over the past years. The initial commercial application in the United States was introduced by Prestige Brands with a benzocaine containing strip marketed under its Chloraseptic® brand. Novartis followed with cough and cold drugs (including the actives dextromethorphan and diphenhydramine) under its Triaminic® brand. Others have followed, including in the ethical drug space, e.g. Meda/Biodelivery Sciences' Onsolis® and Reckitt Benckiser's Suboxone®.
The use of thin films and sheets for buccal and sublingual delivery is a promising area for drug delivery due to, inter alia, the avoidance of first pass metabolism. For such products, it is has been shown that it is desirable to reduce or eliminate the amount of drug which is transported via salivary flow to the GI tract. This observation is, of course, correct. Where the intention is to use buccal, sublingual or other mucosal surface delivery to avoid first pass effect (or for other reasons), one wants to maximize the drug available for absorption at the intended mucosal delivery site and minimize the amount of drug that is available at unintended delivery sites (the GI tract) where first pass metabolism will not be avoided. See Fuisz U.S. Patent Application Publication No. 20090098192 A1 discussing salivary flow, the content of which is hereby incorporated by reference in its entirety.
A known solution to this issue is the use of a bi layer film or sheet. In one embodiment a soluble film layer containing drug is backed by a second insoluble (or less soluble) layer without active drug. A commercial example of this is the Onsolis® product by Biodelivery Sciences International. The less soluble backing layer protects the drug layer from salivary flow dissolution, thereby increasing the degree of drug available for buccal absorption and decreasing the loss of drug to salivary distribution.
Thus, the desirability of bilayer and multilayer film and sheet systems is understood. However, practitioners will appreciate that such systems are more difficult and costly to manufacture than a single layer film or sheet. Typically, two films must be made and then laminated (see Tapolsky U.S. Pat. No. 7,579,019, the content of which is hereby incorporated by reference in its entirety). Or, one may manufacture one film and then cast a second layer on top of it (see Schmidt U.S. Pat. No. 4,849,246, the content of which is hereby incorporated by reference in its entirety). Of these two methods, it appears the Tapolsky method has gained far more traction in terms of actual commercial practice. Either way however, methods involve greater expense and additional steps as compared with single layer film production.